Factors that provide translational control by inhibiting peptide initiation in rabbit reticulocytes and Friend leukemia cells will be isolated and characterized. Special emphasis will be placed on the mechanism by which the primary inhibitors are activated or inactivated and the mechanism by which they cause inhibition. Most, if not all of the inhibitors currently under study appear to directly or indirectly involve cAMP-independent protein kinases. Activation of inhibitors in reticulocyte lysates is carried out by hemin deficiency or by pressure to 15,000 psi. Hemin deficient lysates contain a protein kinase, HCR, for the small subunit of the peptide initiation factor, eIF-2, and a second inhibitor that appears to be associated with protein kinase activity for certain proteins of 40S ribosomal subunits. Pressure treatment of lysates activates two separate components that are distinguishable from either HCR or the 40S ribosome inhibitor. One is a heat stable component of about 30,000 daltons that can be activated by heat as well as pressure. The other is a heat labile factor of about 40,000 daltons. Purification procedures for both of these pressure activated inhibitors are being developed. Techniques developed with the reticulocyte factors will be used to activate, isolate and characterize inhibitory factors in Friend cells. Special emphasis will be placed on the role these factors play in maintaining the transformed state in these virus transformed cells.